Breast and prostate cancers harbor common somatic copy number alterations that consistently differ by race and are associated with survival
Autor: | Benjamin A. Rybicki, Yalei Chen, Indrani Datta, Kanika Taneja, Nilesh S. Gupta, Albert M. Levin, Dhananjay A Chitale, Jia Li, Melissa Davis, Craig G. Rogers, Lisa A. Newman, Sudha M. Sadasivan, Ruicong She, Pamela L. Paris |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Oncology Male lcsh:Internal medicine medicine.medical_specialty Race lcsh:QH426-470 DNA Copy Number Variations Somatic cell Genetic ancestry Breast Neoplasms SCNA 03 medical and health sciences Prostate cancer 0302 clinical medicine Breast cancer Prostate Internal medicine Genetics Biomarkers Tumor Ethnicity Medicine Cluster Analysis Humans Clinical significance lcsh:RC31-1245 Genetics (clinical) business.industry Gene Expression Profiling Racial Groups Chromosome Prostatic Neoplasms Genomics medicine.disease Prognosis Human genetics Gene Expression Regulation Neoplastic Survival Rate lcsh:Genetics 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis SCNAs Female business Research Article |
Zdroj: | BMC Medical Genomics BMC Medical Genomics, Vol 13, Iss 1, Pp 1-15 (2020) |
ISSN: | 1755-8794 |
Popis: | Background Pan-cancer studies of somatic copy number alterations (SCNAs) have demonstrated common SCNA patterns across cancer types, but despite demonstrable differences in aggressiveness of some cancers by race, pan-cancer SCNA variation by race has not been explored. This study investigated a) racial differences in SCNAs in both breast and prostate cancer, b) the degree to which they are shared across cancers, and c) the impact of these shared, race-differentiated SCNAs on cancer survival. Methods Utilizing data from The Cancer Genome Atlas (TCGA), SCNAs were identified using GISTIC 2.0, and in each tumor type, differences in SCNA magnitude between African Americans (AA) and European Americans (EA) were tested using linear regression. Unsupervised hierarchical clustering of the copy number of genes residing in race-differentiated SCNAs shared between tumor types was used to identify SCNA-defined patient groups, and Cox proportional hazards regression was used to test for association between those groups and overall/progression-free survival (PFS). Results We identified SCNAs that differed by race in breast (n = 58 SCNAs; permutation p − 4) and prostate tumors (n = 78 SCNAs; permutation p = 0.006). Six race-differentiated SCNAs common to breast and prostate found at chromosomes 5q11.2-q14.1, 5q15-q21.1, 8q21.11-q21.13, 8q21.3-q24.3, 11q22.3, and 13q12.3-q21.3 had consistent differences by race across both tumor types, and all six were of higher magnitude in AAs, with the chromosome 8q regions being the only amplifications. Higher magnitude copy number differences in AAs were also identified at two of these race-differentiated SCNAs in two additional hormonally-driven tumor types: endometrial (8q21.3-q24.3 and 13q12.3-q21.3) and ovarian (13q12.3-q21.3) cancers. Race differentiated SCNA-defined patient groups were significantly associated with survival differences in both cancer types, and these groups also differentiated within triple negative breast cancers based on PFS. While the frequency of the SCNA-defined patient groups differed by race, their effects on survival did not. Conclusions This study identified race-differentiated SCNAs shared by two related cancers. The association of SCNA-defined patient groups with survival demonstrates the clinical significance of combinations of these race-differentiated genomic aberrations, and the higher frequency of these alterations in AA relative to EA patients may explain racial disparities in risk of aggressive breast and prostate cancer. |
Databáze: | OpenAIRE |
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